SYNTHESIS AND UNUSUAL PROPERTIES OF AN 8,12-BIS-PIVALIC ACID ANALOG OF BILIRUBIN

A sterically congested analog of bilirubin with propionic acid groups replaced by pivalic acids (1) was synthesized from methyl -ethoxycarbo nyl-1H-pyrrol-3-yl)-2-methylpropionate (8). UV-visible and NMR spectro scopic analyses of 1 suggest intramolecularhydrogen-bonding and a pref erence for a ridge-tile conformation. The activation parameters for M reversible arrow P conformational inversion of 1 were determined by dy namic NMR analysis to be Delta H double dagger 19.7 +/- 1.4 kcal/mole and Delta S double dagger +/- 10.4 +/- 4.5 eu. Molecular dynamics comp utations predict a global energy minimum for a somewhat more open ridg e-tile conformation as compared with bilirubin. Circular dichroism of the pigment complex with human serum albumin gives a bisignate Cotton effect: Delta epsilon(431)(max) = -51, Delta epsilon(382)(max) = +30, with the opposite signed order as compared with that found for the par ent mesobilirubin-XIII alpha and bilirubin.